The goals of this research are to develop advanced MRS and imaging techniques and to apply them and other complementary methods to studying brain metabolism, neurotransmission and enzyme activity. MRS allows measurement of neurotransmission of glutamate and GABA in vivo, which play important roles in many major psychiatric diseases including depression and schizophrenia. During 2015-2016, we made significant progress in the development and applications of novel spectroscopic and imaging techniques for studying metabolism and neurotransmission in vivo in the brain. We invented a computational method for quantifying spatially localized MRS data involving multiple nuclear spin systems (Zhang et al, EUROMAR 2016; Aarhus, Denmark.). This method can reduce the time for calculating chemical basis function from days to minutes on a typical desktop personal computer. As such, design and optimization of proton MRS by computers become practical and highly useful. By optimizing localized proton MRS using extensive computation to simultaneously maximize spectral resolution and sensitivity to nuclear spin relaxation we were able to develop a novel technique that can simultaneously measure concentration, longitudinal and transverse relaxation times of many brain chemicals including glutamate in a single scan session with less than ten minutes of MRS data acquisition. This multiparametric approach will allow us to not only measure concentrations but also the microenvironments of, e.g., glutamatergic neurons in a typical clinical setting. Significant progress has also been made in studying glutamate and GABA neurotransmission. In particular, we have made important contributions to characterizing brain chemicals especially glutamate under technically very challenging situations (N. Li, L. An, and J. Shen, Spectral fitting using basis set modified by measured B0 field distribution, NMR Biomed., 28:1707-15 (2015).).